Feldman v. Lederle Laboratories

592 A.2d 1176, 125 N.J. 117, 1991 N.J. LEXIS 80

• Court: Supreme Court of New Jersey
• Decided: July 24, 1991
• Status: Published

Opinions

The opinion of the Court was delivered by

CLIFFORD, J.

In Feldman v. Lederle Laboratories, 97 N.J. 429, 479 A.2d 374 (1984) (Feldman I), we held that under the doctrine of strict products liability, “drug manufacturers have a duty to warn of dangers of which they know or should have known on the basis of reasonably obtainable or available knowledge.” Id. at 434, 479 A.2d 374. At the retrial following our remand, plaintiff argued that Declomycin, an antibiotic manufactured by defendant, Lederle Laboratories (Lederle), had permanently turned her teeth gray, and that the drug had been defective during the years 1960 to 1963 (the time she had used it) because it had lacked a warning that its ingestion by young children might result in tooth staining. Defendant attempted to show that relevant federal statutes and regulations had precluded it from performing its state-law duty to warn, and asserted that it could not be held liable for doing that which the federal law had compelled. The trial court rejected that argument and submitted to the jury plaintiffs strict-liability claim based on failure to warn. On the basis of its finding that Declomycin had not been defective in either 1960 or 1961 but that it had been defective in 1962 and 1963, the jury found in favor of plaintiff and awarded her $300,000.

The Appellate Division, concluding that “the theory of liability which undergirded the jury verdict against Lederle was preempted by federal law,” 234 N.J.Super. 559, 564, 561 A.2d 288 (1989), reversed and remanded the case for entry of judgment in favor of defendant. We granted plaintiff’s petition for certification, 122 N.J. 348, 585 A.2d 360 (1990), to determine whether her strict-liability cause of action based on failure to warn is preempted under the supremacy clause, U.S. Const. art. VI, cl. 2. We hold that in the circumstances of this case federal law does not preempt liability under state law. Consequently, we reverse the judgment of the Appellate Division and remand to that court for consideration of the other issues previously raised on appeal there but not decided. See 234 N.J.Super. at 564-65 n. 3, 561 A.2d 288.

I

—A—

Tetracyclines, a group of antibiotics first introduced in 1948, are used to combat bacterial infections. A primary benefit of tetracyclines is that they are effective against a wider variety of organisms than are other antibiotics. In 1959 Lederle introduced a new tetracycline analogue, demethylchlortetracycline, under the trade name Declomycin. The 1959 edition of the Physicians’ Desk Reference (PDR), an annual used by doctors to determine the appropriate administration and effects of prescription drugs, stated that Declomycin had “greater antibiotic potency that made it possible to achieve therapeutic activity with less weight of antibiotic,” that it had “a reduced renal clearance rate that produced a prolongation of the antibacterial levels in the body,” and that it was “therapeutically equally effective as other tetracyclines in infections caused by organisms sensitive to the tetracyclines.” Feldman I, supra, 97 N.J. at 436, 479 A.2d 374. The description did not mention tooth discoloration as a possible side effect. Ibid. Beginning some time after 1963, the PDR contained a warning that administration of Declomycin during the developmental stage of the permanent teeth — prenatal to approximately seven years of age — could cause permanent tooth discoloration. Ibid.

Plaintiff, Carol Ann Feldman, was born in 1960. Her father, Dr. Harold Feldman, testified that he had treated plaintiff with Declomycin two or three times a year between 1960 and 1963. He had not maintained records of the administrations but said that he had given the antibiotic only nine or ten times during that period. (“Times” refers not to individual administrations but to courses of treatment lasting an indeterminate but brief period.)

Shortly after Declomycin was introduced, Dr. Feldman became acquainted with it through a medical representative employed by Lederle. Dr. Feldman stated that the representative “informed me as to its qualities, to its effectiveness, to how it was being suggested in its use,” and that the representative had left samples with the doctor after telling him “how useful the drug was in treating upper respiratory infections and how that was palatable for children.” The drug had been made available in cherry-flavored pediatric drops and syrup and custard-flavored oral suspension, and in varying forms of packaging, including clown-shaped bottles obviously intended for pediatric use. That no warning of the potential side effect of tooth discoloration accompanied the various forms of packaging of Declomycin prior to December 1963 is not disputed.

Plaintiffs baby teeth were discolored gray-brown. When plaintiffs permanent teeth began to erupt around 1965, Dr. Feldman became concerned because they too were discolored. After the family dentist examined plaintiff, he.informed Dr. Feldman of “the possibility of a correlation between tetracycline and infant tooth staining.” On learning from other physicians that some of them also were experiencing staining of teeth in patients treated with tetracyclines, Dr. Feldman stopped prescribing Declomycin for pediatric use.

No one disputes that the discoloration of plaintiffs teeth is the result of ingestion of tetracycline during the developmental stage of her permanent teeth, nor does defendant contest the jury’s finding that Declomycin was the specific tetracycline involved. Rather, the dispute focuses on what action Lederle could and should have taken on acquiring knowledge of the correlation between the use of tetracyclines, particularly Declomycin, and staining of teeth.

Plaintiff contends that Lederle knew or through the exercise of reasonable diligence should have known of the possible serious and permanent side effects of Declomycin before and at the time she ingested the drug. She also asserts that Lederle “failed and refused to warn the plaintiff, pediatric consumers, and their physicians of those harmful effects in timely, adequate, and reasonable fashion.” As evidence of Lederle’s actual or constructive knowledge, plaintiff introduced at trial an internal Lederle report dated August 28, 1962. The third page of the report, under the heading “Declomycin-Achromycin,” reads:

We are beginning to hear comments about the yellowing discoloration of teeth in children following tetracycline therapy. One physician, already reported to [Lederle’s corporate headquarters], also states his own children’s second teeth are soft following tetracycline therapy. This physician states he will discontinue using tetracyclines until this phenomenon is proven or disproven.

Within three months of that report, Dr. Swanzey, an employee of Lederle from 1955 through the 1970s, wrote a letter to the Food and Drug Administration (FDA) notifying it of the possibility of a correlation between tooth discoloration and tetracycline use. In the letter, dated November 16, 1962, Lederle proposed adding the following warning to the labeling of all its tetracycline products: “Use of any tetracycline during tooth development in the neonatal period or early childhood may cause discoloration of the teeth.” The letter continued: “Your early opinion and consideration is requested in order that this statement may be added at the earliest possible time.”

Dr. Raymond Barzilai, a medical officer with the FDA, responded to Dr. Swanzey’s proposal by letter dated December 3, 1962. He indicated that the FDA had “not yet reached any form of final opinion (= medical, scientific, regulatory, etc.),” and was “currently devoting a great deal of active attention to the matter.” Dr. Barzilai concluded: “[The FDA] will notify you as soon as any conclusion is reached.” One copy of that letter bears a handwritten note suggesting that on its receipt, Lederle requested permission to disseminate the proposed warning in a circular but was “advised” by the FDA not to do so.

On January 15, 1963, Dr. Swanzey wrote to Dr. Barzilai with additional information relating to the possible correlation of tetracycline use and tooth discoloration. He related that he had spoken with a Dr. Zegarelli, who

confirmed that this phenomenon was peculiar to oxytetracycline, tetracycline, and chlortetracycline. He had no experience with demethylchlortetracycline. He felt that some statement is certainly indicated to be included in our package literature but expressed real concern that improper attention or publicity to this phenomenon should be avoided at all costs.

We [Lederle] are conducting some further discussions with others who may have had experience with the use of tetracyclines during the various periods of tooth developments, and based upon this we will arrive at a statement concerning which I will discuss with you later.

By letter dated February 4, 1963, the FDA informed Lederle of the following:

1. After an extensive analytical review of the subject, this Administration has concluded that the effects on bone and teeth caused by the systemic use of the Tetracycline(s) products are clinically substantial and should be properly brought to the attention of the medical profession.

2. At present, the alleged teratogenic effects from tetracycline(s) have not been sufficiently documented as to justify any form of action within our authorized functions.

The following warning statement is being proposed for insertion in the printed matter of all your Tetracycline products:

“Tetracyclines may form a stable calcium complex in any bone forming tissue with no serious harmful effects reported thus far in humans. However, use of any tetracycline drug during tooth development (= last trimester of pregnancy, neonatal period and early childhood) may cause discoloration of the teeth (= yellow-grey-brownish). This effect occurs mostly during long-term use of the drug but it has also been observed in usual short treatment courses .

In closing, I wish to mention that this Administration appreciated your initiative of offering constructive suggestions as well as your cooperative spirit.

On February 14, 1963, Dr. Swanzey agreed to incorporate the FDA’s “suggested statement” in Lederle’s literature and stated: “I assume that this statement is being proposed for chlortetracycline, oxytetracycline and demethylchlortetracycline as well.” He continued:

Before incorporating this in our labeling, however, I would like confirmation from you that it is acceptable to other manufacturers or if appropriate changes are to be made, thereby assuring that these effects common to all of the tetracycline antibiotics will be identical for all products. [Emphasis added.]

A letter of Dr, Barzilai dated February 18, 1963, furnished the requested confirmation:

1. This statement will have to appear only on the labeling for: Tetracycline, Chlortetracycline and Oxytetracycline. There is practically no specific clinical evidence to substantiate such a labeling requirement for Demethylehlortetracycline at present, but we intend to remain alert for such a future possibility.

********

3. At any rate, I see no reasonable ground for any change in the wording of the statement and we [the FDA] expect to see it reproduced as is in the appropriate labelings as soon as possible.

In fact, the text of the warning was changed slightly, as Lederle learned from an FDA letter dated April 12, 1963. That letter went on to state: “We [the FDA] now have information that leads us to believe that this change in labeling should be made immediately. Therefore, we are asking that no further shipments be made of these drugs until the change has been made.” Notably, although the letter displays a sense of urgency with respect to the warning, it, as well as other correspondence submitted by defendant, casts the FDA in a passive role. No change in the exception for Declomycin is indicated. That status was confirmed by a FDA press release issued April 18, 1963, which read in part: “ ‘There is no evidence to date that a fourth drug, demethylchlortetracycline, causes the discoloration,’ FDA said.” In fact there was such evidence at that time, as indicated by subsequent correspondence, although that evidence may not then have been available to the FDA.

In response to the exchange with the FDA, Lederle issued a memorandum to all its salespeople - on April 23, 1963. With respect to Declomycin, the memorandum stated:

You will note that DECLOMYCIN is not included in the list of tetracycline analogues involved in this current revision. Therefore, the inserts and stickers are not to be attached to DECLOMYCIN circulars and literature. While DECLOMYCIN has not been officially implicated with tooth staining, it probably will be within a short period of time, therefore, any gain by making an issue of this fact would rebound unfavorably at a later date. In the meantime, in answer to any questions from a doctor concerning DECLOMYCIN and tooth staining, your answer is, “DECLOMYCIN has not as yet been officially implicated with tooth staining.” [Emphasis added.]

Significantly, that response by Lederle does not indicate any intention to prevent or curtail use of Declomycin by the at-risk group; nor does there appear to have been any consideration given to suspending production of Declomycin in the form of flavored pediatric drops, syrup, or oral suspension pending the probable implication of Declomycin with tooth staining. The answer to be given inquiring physicians can be described accurately as evasive.

Lederle continued to correspond with the FDA regarding the possibility of a correlation between Declomycin and tooth staining. That correspondence, however, did not attempt to convince the FDA that a warning for Declomycin was necessary. Rather, on May 8, 1963, Dr. Swanzey submitted additional information to the FDA with a letter stating: “This is our total experience to date and is certainly still insufficient to establish clearly that demethylchlortetracycline may cause tooth staining. It is probably premature to conclude that a warning in labeling is indicated.”

- Enclosed with that letter were publications and reports from practitioners strongly suggesting a correlation between Declomycin — as distinguished from tetracycline drugs in general— and tooth staining. The majority of those reports were in the possession of Lederle or its affiliates in 1962, with the most recent report being submitted to Cyanamid of Canada Limited (an affiliate of Lederle) in January 1963. The responsive letter from Cyanamid, dated February 1,1963, stated in part: “At the present time and with the information available, it can only be postulated that the discolouration has indeed been the result of Declomycin administration, and one must admit that there appears to be a likely association.”

On May 31, 1963, FDA Commissioner George Larrick wrote to Dr. Swanzey regarding the warning and labeling change for tetracycline drugs. With respect to Declomycin he stated: “Actually, the original statement was revised to require the inclusion of the name of the drug in lieu of the word ‘tetracyclines’ because to date we have no evidence that your drug demethylchlortetracycline will stain teeth. If the warning statement as originally proposed is used, it automatically incriminates demethylchlortetracycline.”

On July 1,1963, Dr. Barzilai, responding to Lederle’s letter of May 8th, stated:

We have reviewed your information and we believe that it cannot as yet justify any change in our current formal position on this matter.

You will realize, of course, that we need unequivocal factual evidence of adverse reaction in man to substantiate any official regulatory decision or action. Dr. Annett’s case is only “suggestive” but, since grossly similar brown dental staining has long been observed in conditions other than Tetracycline treatment (cystic fibrosis is an example), this case would require further analysis by proper means (chemical, fluorescence, etc.) to eventually detect and identify the Tetracycline analogue.

Your information will be filed in our records for future reference and be assured that we are following the development of this matter with utmost interest.

The record is silent on whether at any time Lederle undertook “further analysis by proper means” to confirm the suggested adverse reaction.

On November 11, 1963, Lederle’s J. Kevin Rooney wrote to Dr. Barzilai that the manufacturer would incorporate a tooth-staining warning statement in all of its labeling for demethylchlortetracycline products. That letter was apparently a confirmation of a prior conversation authorizing the labeling change. The record does not reveal what additional information, if any, was brought to the FDA’s attention in order to justify the change in its “current formal position.” Lederle submitted the revised labeling in December 1963 and incorporated it into the packaging of Declomycin shortly thereafter. The record contains no correspondence from the FDA reflecting its authorization of a change in labeling or its approval of the revised labeling submitted.

In 1975, Dr. Feldman wrote Lederle regarding the discoloration side effect. Lloyd S. Carr, then Lederle’s Product Service Manager, replied in a letter stating that after “the causal relationship between tooth staining and tetracycline [had been] unquestionably demonstrated,” Lederle had notified the FDA in November 1962 requesting permission to place a warning re-' garding discoloration on the labeling. Carr’s letter went on to indicate that in April 1963 the FDA had “directed all manufacturers of tetracycline to include appropriate warnings in their labeling” but that Declomycin had been specifically excluded.

—B—

Plaintiff, through her father as guardian ad litem, filed suit in 1978 against Lederle and its parent corporation, American Cyanamid Company, seeking recovery under theories of negligence, gross negligence, breach of express and implied warranties, and strict products liability, among others. She alleged that Declomycin had been defective as marketed during the period when she had ingested the drug. A jury returned a verdict for defendant in 1980, and the Appellate Division affirmed in an unreported opinion. This Court granted plaintiff’s petition .for certification and summarily remanded the cause to the Appellate Division, 91 N.J 266, 450 A.2d 579 (1982), for reconsideration in light of Beshada v. Johns-Manville Products Corp., 90 N.J. 191, 447 A.2d 539 (1982). The Appellate Division again affirmed, 189 N.J. Super. 424, 460 A.2d 203 (1983), holding that Beshada did not apply and that prescription drugs are so important to society that suppliers should not be subject to strict liability. This Court granted a second petition for certification, 94 N.J. 594, 468 A.2d 230 (1983), and reversed and remanded for a new trial, holding that prescription drug manufacturers are not immune from strict-liability claims. Feldman I, supra, 97 N.J. 429, 479 A.2d 374.

At the second trial in 1985 Lederle moved at the close of the evidence to dismiss the complaint on the basis of preemption. More specifically, it claimed that federal regulations in effect at the time of marketing and plaintiffs injury did not permit it to warn about the possibility of tooth staining without prior approval of the FDA. According to Lederle, compliance with the obligation under New Jersey law to communicate a warning based on subsequently-acquired actual or constructive knowledge of a danger “as soon as reasonably feasible,” Feldman I, supra, 97 N.J. at 456, 479 A.2d 374, would have placed it in violation of federal regulations if the warning had been given without prior FDA approval. Lederle contended, therefore, that plaintiff's claim is preempted.

The court denied the motion, holding that the regulations at issue were not mandatory but discretionary, and

[did] not in any way bar a drug manufacturer from, in accordance with the language of Feldman [I], putting out adequate warnings when information indicating that the product may be dangerous to the public comes to that drug manufacturer’s attention.

********

I am not satisfied that the defendant has in this record presented to the Court anything that would change the Opinion of the New Jersey Supreme Court in [Feldman I] to the effect that this area has been pre-empted by the Federal Government.

The court noted specially that Lederle had cited no administrative decisions or case law construing the regulation to be mandatory. Moreover, the court observed that Dr. Goddard, the commissioner of the FDA from 1966 to 1968, had testified at a hearing pursuant to Evidence Rule 8 that the FDA had not been enforcing labeling regulations prior to his tenure as commissioner.

The jury returned a verdict for plaintiff on the sole count— alleging strict liability for failure to warn — of her amended complaint that the court had submitted. The verdict form reflected the following specific findings:

1. Plaintiff ingested Declomycin between 1960 and 1963.

2. There was not a defect in Declomycin because it failed to warn of tooth discoloration in 1960 and in 1961.

3. There was a defect in Declomycin because it failed to warn of tooth discoloration in 1962 and in 1963.

4. The failure to warn was a proximate cause of plaintiff’s losses and injuries.

Lederle renewed its motion for judgment pursuant to Rule 4:40-2(b), and the trial court again denied the motion.

On appeal, Lederle continued to assert that plaintiffs claim based on failure to warn is preempted by federal laws and regulations governing labeling of antibiotics and prescription drugs. The Appellate Division reversed and remanded for entry of judgment in favor of Lederle:

We conclude that the Food and Drug Administration’s (FDA) regulation of the drug industry does not warrant a finding of implied federal preemption of all State tort claims grounded in strict liability failure to warn. However, under certain circumstances, such as presented here, federal law may preempt a discrete issue upon which liability is predicated because compliance with State decisional law would require federal law to be violated. Thus, plaintiff’s entire cause of action was not preempted. However, the theory of liability not preempted was decided adversely to plaintiff by the jury and is not challenged on appeal, while the theory of liability which undergirded the jury verdict against Lederle was preempted by federal law. Thus, Lederle’s motion for judgment notwithstanding the verdict should have been granted. [234 N.J.Super. at 564, 561 A.2d 288.]

From that ruling plaintiff petitioned for certification, which we granted. 122 N.J. 348, 585 A.2d 360 (1990). Plaintiff presents two distinct issues. First, she contends that the Appellate Division was bound by what she claims this Court decided in Feldman I, namely, that plaintiffs striet-liability claim based on failure to warn is not preempted by federal law. Second, plaintiff argues that even if the Appellate Division was free to consider the issue of preemption, its conclusion that plaintiffs claim is preempted by federal law was erroneous.

II

The first issue is whether the Appellate Division was free to address the issue of preemption at all. Plaintiff contends that in Feldman I this Court determined that a cause of action based on failure to warn was not preempted by FDA regulations governing the labeling of prescription drugs. According to plaintiff, the Appellate Division was consequently precluded by the law-of-the-case doctrine from reconsidering the issue after remand.

The law-of-the-case doctrine is a guide for judicial economy based on the sound policy that “when an issue is once litigated and decided during the course of a * * * case, that decision should be the end of the matter.” State v. Hale, 127 N.J.Super. 407, 410, 317 A.2d 731 (App.Div.1974) (citing United States v. United States Smelting, Ref. & Mining Co., 339 U.S. 186, 198, 70 S.Ct. 537, 544, 94 L.Ed. 750, 760-61 (1950)). Plaintiffs argument, however, is more accurately considered as one of precedent and supremacy. If this Court had conclusively resolved the preemption issue in Feldman I, that determination would not have been open to re-examination by the lower courts on remand. See Liptak v. Frank, 206 N.J.Super. 336, 338-39, 502 A.2d 1147 (App.Div.1985), certif. denied, 103 N.J. 471, 511 A.2d 652 (1986); In re Educ. Ass’n, 117 N.J.Super. 255, 261, 284 A.2d 374 certif. denied, 60 N.J. 198, 287 A.2d 458 (1972). However, the precedential effect of an opinion depends on the court’s intention to resolve an issue squarely presented. See, e.g., Lehigh Valley R.R. v. Chapman, 35 N.J. 177, 187, 171 A.2d 653, cert. denied, 368 U.S. 928, 82 S.Ct. 364, 7 L.Ed.2d 192 (1961). Our analysis, therefore, necessarily turns to a determination of what we did — and did not — intend to resolve in Feldman I.

In Feldman I this Court noted that on the summary remand to the Appellate Division, defendant had raised for the first time the claim that federal regulations prohibited it from fulfilling its duty to warn because they precluded it from modifying its labeling without prior FDA approval. 97 N.J. at 458, 479 A.2d 374. The issue of federal preemption had been neither raised nor addressed at the first trial. Ibid. Consequently, Lederle had not presented evidence that FDA regulations had prevented it from warning as soon as it became aware of the necessity. Id. at 446-47, 479 A.2d 374. We stated: “Under these circumstances we would ordinarily defer discus-' sion of the issue. However, since the trial court may be faced with the problem on the retrial, * * * some comments are in order.” Id. at 458, 479 A.2d 374 (emphasis added).

In contrast, we stated in a footnote to the antecedent paragraph, addressing the proper jury charge on the obligation to warn to be used at the retrial, that

plaintiff did not object to the charge and did not raise this issue on her initial appeal. Since the cause must be retried, * * * and the issue was raised and argued before us, we have decided the question. [Id. at 458 n. 7, 479 A.2d 374 (emphasis added).]

The quoted and emphasized language establishes that this Court was not at a loss for precise expression when declaring the weight that should be accorded its pronouncements. The language of Feldman I taken in its entirety clearly indicates that it was not intended to resolve the preemption issue and therefore did not preclude defendant from making its preemption argument, with additional proofs, on remand. See United States Smelting, Ref. & Mining Co., supra, 339 U.S. at 198, 70 S.Ct. at 544, 94 L.Ed. at 760-61.

Ill

The more substantial issue is whether the Appellate Division correctly decided that plaintiffs cause of action based on failure to warn is preempted because of actual conflict with the obligations imposed by federal laws and regulations in effect at the time of distribution and ingestion. We conclude that plaintiffs cause of action is not preempted, there being no direct conflict with federal law.

The preemption doctrine, rooted in the second clause of article VI of the United States Constitution, requires that when the mandates of federal law and state law are not consistent, the state law must yield. See Wisconsin Pub. Interventor v. Mortier, — U.S. -, -, 111 S.Ct. 2476, 2481, 115 L.Ed.2d 534 (1991). Federal regulations have the same preemptive effect as federal statutes. Hillsborough County v. Automated Medical Laboratories, Inc., 471 U.S. 707, 713, 105 S.Ct. 2371, 2375, 85 L.Ed.2d 714, 721 (1985); Capital Cities Cable, Inc., v. Crisp, 467 U.S. 691, 699, 104 S.Ct. 2694, 2700, 81 L.Ed.2d 580, 589 (1984). Furthermore, the doctrine applies equally to state common law and state statutory law. Chicago N. W. Transp. Co. v. Kalo Brick & Tile Co., 450 U.S. 311, 325-26, 101 S.Ct. 1124, 1134, 67 L.Ed.2d 258, 270 (1981).

Preemption may occur in several ways. Provided Congress or the federal agency is acting within the scope of its authority, express language may exclude state law. Schneidewind v. ANR Pipeline Co., 485 U.S. 293, 299, 108 S.Ct. 1145, 1150, 99 L.Ed.2d 316, 325 (1988). In the absence of a clear expression, the “intent to preempt all state law in a particular area may be inferred where the scheme of federal regulation is sufficiently comprehensive to make reasonable the inference that Congress ‘left no room’ for supplementary state regulation.” Hillsborough County, supra, 471 U.S. at 713, 105 S.Ct. at 2375, 85 L.Ed.2d at 721 (quoting Rice v. Santa Fe Elevator Corp., 331 U.S. 218, 230, 67 S.Ct. 1146, 1152, 91 L.Ed. 1447, 1459 (1947)). Where “the object sought to be obtained by federal law and the character of obligations imposed by it may reveal the same purpose,” the intent to preempt state law will be inferred. Rice, supra, 331 U.S. at 230, 67 S.Ct. at 1152, 91 L.Ed. at 1459. A third situation in which preemption will be implied occurs when “ ‘the Act of Congress may touch a field in which the federal interest is so dominant that the federal system will be assumed to preclude enforcement of state laws on the same subject.’ ” Fidelity Fed. Sav. & Loan Ass’n v. de la Cuesta, 458 U.S. 141, 153, 102 S.Ct. 3014, 3022, 73 L.Ed.2d 664, 675 (1982) (quoting Rice, supra, 331 U.S. at 230, 67 S.Ct. at 1152, 91 L.Ed. at 1459).

Conflict preemption occurs when “compliance with both federal and state regulations is a physical impossibility,” Florida Lime & Avocado Growers, Inc. v. Paul, 373 U.S. 132, 142-43, 83 S.Ct. 1210, 1217, 10 L.Ed.2d 248, 257 (1963), or when state law “stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” Hines v. Davidowitz, 312 U.S. 52, 67, 61 S.Ct. 399, 404, 85 L.Ed. 581, 587 (1941). Once the impossibility of dual compliance is established, the importance to the State of its own law is immaterial. Felder v. Casey, 487 U.S. 131, 138, 108 S.Ct. 2302, 2306, 101 L.Ed.2d 123, 138 (1988); Brown v. Hotel Employees & Bartenders Int’l Union Local 54, 468 U.S. 491, 503, 104 S.Ct. 3179, 3186, 82 L.Ed.2d 373, 384 (1984). When there is a conflict, “the federal law must prevail.” Free v. Bland, 369 U.S. 663, 666, 82 S.Ct. 1089, 1092, 8 L.Ed.2d 180, 183 (1962); see also de la Cuesta, supra, 458 U.S. at 153, 102 S.Ct. at 3022, 73 L.Ed.2d at 675 (“state law is nullified to the extent that it actually conflicts with federal law”). The conflict, however, must be actual, not merely potential, speculative, or hypothetical. Rice v. Norman Williams Co., 458 U.S. 654, 659, 102 S.Ct. 3294, 3299, 73 L.Ed.2d 1042, 1049 (1982).

In de la Cuesta, the Supreme Court addressed an alleged conflict between regulations issued by the Federal Home Loan Bank Board (Board) that authorized due-on-sale clauses (clauses that grant a lender the option to demand immediate payment of the loan balance if the subject property is sold or transferred without the lender’s consent) in the loan contracts of federal savings and loan associations, and provisions of the California Civil Code that had been interpreted by the state to limit enforceability of such clauses. The Court found both a clear and manifest expression of an intent to preempt and an actual conflict:

[California law] explicitly bars a federal savings and loan from exercising a due-on-sale clause to adjust a long-term mortgage’s interest rate towards current market rates — a due-on-sale practice the Board has approved and views as critical to “financial stability of the association.” [458 U.S. at 156, 102 S.Ct. at 3024, 73 L.Ed.2d at 677.]

Because the Court also found that the Board was acting within its authority, the conflicting state regulations limiting due-on-sale practices of federal associations were preempted.

In contrast, in Silkwood v. Kerr-McGee Corp., 464 U.S. 238, 104 S.Ct. 615, 78 L.Ed.2d 443 (1984), the Court found that the Atomic Energy Act and its enacting regulations did not preclude an award of punitive damages under state law. The Court recognized that states had been expressly prohibited from regulating the safety aspects of hazardous materials, but refused to extend that prohibition to state-law remedies for persons injured from radiation exposure in nuclear plants. Id. at 250-51, 104 S.Ct. at 622-23, 78 L.Ed.2d at 453-54. The Court rejected the contention that the award of damages would conflict with the federal remedial scheme, finding that “[pjaying both federal fines and state-imposed punitive damages for the same incident would not appear to be physically impossible.” Id. at 257, 104 S.Ct. at 626, 78 L.Ed.2d at 458. It concluded that

the provision cited by Kerr-McGee goes on to state that atomic energy should be developed and utilized only to the extent it is consistent "with the health and safety of the public.” 42 U.S. C. § 2013(d). Congress therefore disclaimed any interest in promoting the development and utilization of atomic energy by means that fail to provide adequate remedies for those who are injured by exposure to hazardous nuclear materials. [Ibid..]

The Supreme Court has since unanimously confirmed that “ ‘[ojrdinarily, state causes of action are not pre-empted solely because they impose liability over and above that authorized by federal law.’ ” English v. General Elec. Co., — U.S. -, -, 110 S.Ct. 2270, 2280, 110 L.Ed.2d 65, 81 (1990) (quoting California v. ARC Am. Corp., 490 U.S. 93, 105, 109 S.Ct. 1661, 1667, 104 L.Ed. 2d 86, 97 (1989) (seven justices participating)). Furthermore, as stated in English, “[tjhe ‘teaching of this Court’s decisions * * * enjoin[s] seeking out conflicts between state and federal regulation where none clearly exists.’ ” Id. at -, 110 S.Ct. at 2281, 110 L.Ed.2d at 81 (quoting Huron Portland Cement Co. v. City of Detroit, 362 U.S. 440, 446, 80 S.Ct. 813, 817, 4 L.Ed.2d 852, 858 (1960)).

Although “any state law, however clearly within a State’s acknowledged power, which interferes with or is contrary to federal law, must yield,” Free, supra, 369 U.S. at 666, 82 S.Ct. at 1092, 8 L.Ed.2d at 183, the initiation point of the preemption analysis depends on the area of law involved. Because plaintiff’s claims concern rights and remedies traditionally defined solely by state law, namely, tort compensation, defendant here must overcome a presumption against preemption:

When Congress legislates in a field traditionally occupied by the States, “we start with the assumption that the historic police powers of the States were not to be superseded by the Federal Act unless that was the clear and manifest purpose of Congress.” [California v. ARC Am, Corp., supra, 490 U.S. at 101, 109 S.Ct. at 1665, 104 L.Ed.2d at 94 (quoting Rice v. Santa Fe Elevator Corp., supra, 331 U.S. at 230, 67 S.Ct. at 1152, 91 L.Ed. at 1459); accord Mortier, supra, — U.S. at-, 111 S.Ct. at 2481, (adopting initial assumption stated in Rice “[w]hen considering pre-emption”); see also Hillsborough County, supra, 471 U.S. at 715, 105 S.Ct. at 2376, 85 L.Ed.2d at 722 (recognizing a “presumption that state or local regulation of matters related to health and safety is not invalidated under the Supremacy Clause”).]

In Silkwood, the Court emphasized the absence of evidence that Congress had intended to preempt state-law claims or that it had even considered the issue. That absence of a clear and manifest purpose to preempt took on “added significance in light of Congress’ failure to provide any federal remedy for persons injured by such [illegal] conduct.” 464 U.S. at 251, 104 S.Ct. at 623, 78 L.Ed.2d at 454.

We recently considered preemption of a claim “traditionally defined solely by state law” — a strict-liability claim based on failure to warn — in Dewey v. R.J. Reynolds Tobacco Co., 121 N.J. 69, 577 A.2d 1239 (1990). In Dewey this Court rejected the argument that preemption was necessary because the incidental regulatory pressure exerted by a jury verdict would conflict with the Cigarette Act’s secondary goal of uniform regulation. Id. at 88-94, 577 A.2d 1239. Quoting Silkwood, we determined that such incidental regulatory effect does not necessarily create a conflict sufficient to require preemption, even where direct state regulation is preempted expressly:

“It may be that the award of damages based on the state law of negligence or strict liability is regulatory in the sense that a nuclear plant will be threatened with damages liability if it does not conform to state standards, but that regulatory consequence was something that Congress was quite willing to accept.” [Id. at 89, 577 A.2d 1239 (quoting Silkwood, supra, 464 U.S. at 256, 104 S.Ct. at 625, 78 L.Ed.2d at 457).]

Turning to an analysis of the actual regulatory effect that the imposition of state-law liability would have, this Court identified three options for the cigarette manufacturer: (1) “voluntarily” adding an additional warning, (2) adding an insert, and (3) “choosing to do nothing and risking exposure to liability.” Id. at 90, 577 A.2d 1239. Hence, the manufacturer would not be compelled to act in contradiction of the federal labeling requirement that expressly prohibits mandatory state labeling regulations. Furthermore, we stated that even if the manufacturer could not alter its label, a jury could conclude that the manufacturer nevertheless should bear the loss that could have been prevented with a more detailed warning label. Id. at 91-92, 577 A.2d 1239; see also Ferebee v. Chevron Chem. Co., 736 F.2d 1529, 1541 (D.C.Cir.) (“Even if Chevron could not alter the label, Maryland could decide that, as between a manufacturer and an injured party, the manufacturer ought to bear the cost of compensating for injuries that could have been prevented with a more detailed label than that approved by the EPA”), cert. denied, 469 U.S. 1062, 105 S.Ct. 545, 83 L.Ed.2d 432 (1984). But see Papas v. Upjohn Co., 926 F.2d 1019 (11th Cir.1991) (available on Westlaw, CTA11 database, 1991 WL 25740) (holding state tort actions for inadequate warning preempted by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and its enacting regulations). This Court noted in Dewey that FIFRA, the statute addressed in Ferebee and Papas, also contained a preemption clause presumably intended to promote uniformity of labeling, and agreed with the court in Ferebee that the existence of such a goal did not necessarily require a finding of preemption. 121 N.J. at 92, 577 A.2d 1239; cf. Burch v. Amsterdam Corp., 366 A.2d 1079, 1085 (D.C.1976) (manufacturer of hazardous substance not immune from liability based on inadequate warning even though Federal Hazardous Substance Act precludes a state requirement unless such requirement is identical to the warning established by the Act); MacDonald v. Ortho Pharmaceutical Corp., 394 Mass. 131, 139-40, 475 N.E. 2d 65, 70-71 (compliance with FDA-approved labels does not immunize manufacturers from liability despite implied goal of precise and nationally-uniform labeling), cert. denied, 474 U.S. 920, 106 S.Ct. 250, 88 L.Ed.2d 258 (1985).

Adopting here the reasoning of Dewey, we agree with the Appellate Division that plaintiffs claim is not preempted expressly or by implication. We diverge, however, from the Appellate Division’s reasoning that that claim is barred because of a direct conflict between obligations imposed by federal law and those under state tort law. We did not reach that issue in Dewey. See 121 N.J. at 86, 577 A.2d 1239. We also recognize that preemption in the regulation of prescription drugs raises somewhat different concerns from those related to regulating cigarettes that we addressed in Dewey. We therefore consider the reasoning of other jurisdictions that have addressed preemption in the context of FDA and similar regulations and focus our analysis on conflict preemption, specifically that body of case law addressing impossibility of dual compliance.

The Appellate Division adopted the reasoning of Hurley v. Lederle Laboratories Division of American Cyanamid, 851 A.2d 1536, modified, 863 A.2d 1173 (5th Cir.1988), in concluding that plaintiff’s warning claims were preempted due to conflict with obligations under federal law. See 234 N.J.Super. at 591-92, 561 A.2d 288. In Hurley, the plaintiff alleged the failure to warn adequately of the possible severe adverse reactions to a vaccine and the production and marketing of an unreasonably-dangerous product. The district court granted partial summary judgment in favor of Lederle, finding that the Federal Food, Drug and Cosmetic Act of 1938 (FDCA), the Public Health Service Act (PHSA), and the regulations enacting them preempted any state-law claims based on defective design of the vaccine or on the inadequacy of its warning label. Hurley, supra, 851 F.2d at 1538.

Although the Fifth Circuit reversed and remanded, the court, in addressing conflict preemption, stated that the regulations at issue provide that the FDA determines a warning it deems appropriate and “[m]ost importantly], the manufacturers cannot change the language * * * without FDA approval.” Id. at 1542. The court then concluded that

[i]t would be patently inconsistent for a state then to hold the manufacturer liable for including that precise warning when the manufacturer would otherwise be liable for not including it. Thus, assuming that the FDA has processed all the relevant and available information in arriving at the prescribed warning, its decision as to the proper wording must preempt by implication that of a state. [Ibid.]

The court limited the inquiry on remand to whether Lederle had withheld information from the FDA; “[otherwise, the FDA-approved warning is sufficient.” Id. at 1543.

In Abbot v. American Cyanamid Co., 844 F.2d 1108, cert. denied, 488 U.S. 908, 109 S.Ct. 260, 102 L.Ed.2d 248 (1988), the Fourth Circuit was faced with the same issue presented in Hurley, namely, preemption of defective-design and failure-to-warn claims by FDA regulations governing vaccines. That court reversed the district court’s finding of preemption, rejecting as its bases the comprehensiveness of the federal scheme and frustration of purpose. Id. at 1112-14. The Fourth Circuit also rejected the district court’s determination that the warning given by the defendant was adequate as a matter of law despite acknowledging that the labeling “once approved, cannot be changed without FDA approval.” Id. at 1112, 1115 (“adequacy of a warning is a question of fact for the jury”).

In Mazur v. Merck & Co., 742 F.Supp. 239 (E.D.Pa.1990), the defendant asserted that the pervasive scheme regulating all aspects of vaccines compelled a finding of implied preemption. The court disagreed, despite finding that: (1) the regulation of vaccines is comprehensive; (2) the FDA had approved the package insert disseminated by the defendant and alleged to be inadequate; (3) the vaccine labeling must receive federal approval; and (4) the language of the labeling cannot be changed without authorization of the FDA. Id. at 244-46. Noting the strong presumption against preemption both of state tort remedies and in areas of health and safety, and recognizing that preemption would leave Pennsylvania citizens harmed by vaccines without a state tort remedy, that court agreed “with the great majority of courts addressing this issue that Congress did not impliedly preempt state regulation of vaccine manufacture, distribution, and labeling.” Id. at 246 (footnote listing other cases in which no preemption was found omitted). See generally Annotation, Federal Pre-emption of State Common-Law Products Liability Claims Pertaining to Drugs, Medical Devices, and Other Health-Related Items, 98 A.L.R.Fed. 124 (1990) (collecting cases).

The court also rejected the defendant’s narrower conflict-preemption argument based on two observations equally appropriate to the circumstances here:

[M]ere compliance with an FDA suggestion, or for that matter, regulation or order, does not mean that state tort law becomes irrelevant. First, compliance with an FDA regulation may establish that the manufacturer met the appropriate minimum standards of due care, but compliance does not necessarily absolve the manufacturer of all liability. See, e.g., Brochu v. Ortho Pharmaceutical Corp., 642 F.2d 652, 658 (1st Cir.1981). Manufacturers must meet state safety requirements, whether codified or embodied in the common law, in addition to satisfying the initial FDA requirements.

Second, federal regulation serves a very different purpose [from] state tort law. Essentially, federal regulation serves a deterrent purpose by limiting the manufacture of inherently dangerous products to those applicants who meet certain stringent safety standards, while state tort law serves the equally important purpose of compensating individuals injured by those very same products. [Because] compliance with FDA regulations will not ensure that a manufacturer’s products will not cause injury, compliance will not necessarily exempt a manufacturer from liability. When those products do cause injuries, the state tort system provides a means of compensation. State tort law is intended to supplement federal regulation by providing a vehicle for compensation of vaccine-related injuries. [Id. at 247 (footnote omitted) (emphasis added).]

In Ferebee v. Chevron Chemical Co., supra, 736 F.2d 1529, the issue was whether the extensive regulation of paraquat by the Environmental Protection Agency (EPA) and compliance therewith by a manufacturer precluded an inadequate-warning claim under Maryland law. Chevron contended that because the EPA, after careful consideration, had approved the labeling of the paraquat used by the plaintiff, the jury was bound by the EPA’s determination and therefore could not find the labeling inadequate. Id. at 1540.

The court disagreed, reasoning that state tort law may have distinct and “broader compensatory goals.” Ibid.

[Conceivably, a label may be inadequate under state law if that label, while sufficient under a cost-benefit standard, nonetheless fails to warn against any significant risk. In addition, even if the ultimate purposes of federal and state law in this area are the same, a state (acting through its jurors) may assign distinct weight to the elements which go into determining whether a substance as labelled is of sufficient net benefit as to warrant its use.

[I]t need not be the case, as Chevron apparently assumes, that the company can be held liable for failure to warn only if the company could actually have altered its warning. * * * Maryland could decide that, as between a manufacturer and an injured party, the manufacturer ought to bear the cost of compensating for those injuries that could have been prevented with a more detailed label than that approved by the EPA. * * * Chevron can comply with both federal and state law by continuing to use the EPA-approved label and by simultaneously paying damages to successful tort plaintiffs such as Mr. Ferebee. [Id. at 1540-41.]

The Eleventh Circuit rejected the reasoning of Ferebee in Papas v. Upjohn Co., supra, 926 A.2d 1019, holding that “FIFRA impliedly preempts state common law tort suits against manufacturers of EPA-registered pesticides to the extent that such actions are based on claims of inadequate labeling.” Id. at 1024-25 (footnote omitted). That court found preemption on several bases, including a direct conflict via a jury determination of inadequate warning with the EPA’s determination that the labeling is adequate and with “the Congressional intent that the EPA Administrator determine the reasonableness of the risks to man and the environment posed by pesticides.” Id. at 1025. It also noted that the federal district courts are split on the issue. See id. at 1021 n. 1 (collecting cases). The split among courts addressing the issue suggests that there is not a “clear and manifest” expression of congressional intent and calls into question the reasoning and authority of Papas.

Those cases finding preemption based on direct conflict typically have involved patently-incompatible affirmative obligations under federal and state laws. An example is Grocery Manufacturers of America, Inc. v. Gerace, 755 F.2d 993 (2d Cir.), aff'd, 474 U.S. 801, 106 S.Ct. 36, 88 L.Ed.2d 29 (1985). In Gerace the plaintiff contended that New York regulations requiring use of “imitation” on labeling of cheese products directly conflicted with “imitation” as defined for use by federal regulations promulgated pursuant to the FDCA. Compliance with the state regulations would subject a manufacturer to liability for misbranding under federal regulations. The court agreed that compliance with both state and federal law was impossible and held the former to be preempted as applied to the specific area of “imitation” cheese. Id. at 1001.

In Cosmetic, Toiletry & Fragrance Association v. Minnesota, 440 F.Supp. 1216 (D.Minn.1977), aff'd, 575 F.2d 1256 (8th Cir.1978), the court was faced with federal and state labeling requirements for chlorofluorocarbons. The state statute and the FDA regulation required identical labels but differed on the location. Id. at 1219. Addressing the issue at the preliminary-injunction stage, the court found that the plaintiffs, who contended that the state regulations were invalid, had shown a substantial likelihood of success at trial on the preemption issue. Id. at 1225. It therefore issued the injunction. Id. at 1219.

We also note that in both Gerace and Cosmetic, Toiletry & Fragrance Association the purpose of the state enactment was regulatory rather than compensatory. Here, the obligations under federal and state law are neither patently incompatible nor inconsistent regulatory efforts to accomplish the same purpose. See English v. General Elec. Co., supra, — U.S. at -, 110 S.Ct. at 2280, 110 L.Ed.2d at 81; Silkwood, supra, 464 U.S. at 263-64, 104 S.Ct. at 629, 78 L.Ed.2d at 462 (Blackmun, J., dissenting).

—fi-

Turning our attention to this case, we begin by identifying the relevant state and federal laws operating in the field being considered. See Chamber of Commerce of the United States v. State, 89 N.J. 131, 142, 445 A.2d 353 (1982). Under New Jersey law a manufacturer is strictly liable for damages resulting from use of its products when the manufacturer fails to produce and distribute a product that is fit, suitable, and safe for its foreseeable purposes. See Feldman I, supra, 97 N.J. at 450, 479 A.2d 374. A product may be unsafe, and therefore defective, because of a failure to warn or an inadequate warning. Freund v. Cellofilm Properties, Inc., 87 N.J. 229, 242, 432 A.2d 925 (1981). A manufacturer is obligated to communicate a warning based on subsequently-acquired knowledge of a danger “as soon as reasonably feasible.” Feldman I, supra, 97 N.J. at 456, 479 A.2d 374. “Generally speaking, the doctrine of strict liability assumes that enterprises should be responsible for damages to consumers resulting from defective products regardless of fault.” Id. at 450, 479 A.2d 374. When liability is premised on the failure to warn or an inadequate warning, the issue becomes whether the manufacturer knew or could have known of the danger and, if so, whether it “acted in a reasonably prudent manner in marketing the product or in providing the warnings given.” Id. at 451-52, 479 A.2d 374. Under that standard negligence and strict liability in failure-to-warn cases may be deemed to be functional equivalents. Id. at 452, 479 A.2d 374.

The manufacture, sale, and marketing of prescription drugs is extensively regulated by the FDA pursuant to the FDCA and its many amendments and enacting regulations. Specifically, section 331 of Title 21 of the United States Code prohibits the introduction into interstate commerce of any drug that is misbranded. A drug is deemed to be misbranded “[i]f its labeling is false or misleading in any particular,” 21 U.S. C.A. § 352(a), if its labeling does not bear “adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health,” id. § 352(f), or if it is an antibiotic drug, “unless (1) it is from a batch with respect to which a certificate or release has been issued pursuant to section 357 of this title, and (2) such certificate or release is in effect with respect to such drug.” Id. § 352(l). For new drugs the federal scheme has a separate provision that “[n]o person shall introduce * * * into interstate commerce any new drug[ ] unless an approval of an application filed pursuant to subsection (b) of this section is effective with respect to such drug.” Id. § 355(a). The approval process includes review of the proposed labeling. The FDA will deny or withdraw approval if the “labeling is false or misleading in any particular” or “contains any untrue statement of material fact,” or if “there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling.” Id. § 355(d) and (e).

As used in this subsection and subsection (e) of this section, the term “substantial evidence” means evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof. [7d § 355(d).]

Those statutory provisions are augmented by regulations for enforcement of the FDCA and for certification of antibiotic drugs. Lederle claims that the versions of those regulations in effect at the relevant time did not permit it, without prior approval of the FDA, to warn about the possibility of tooth staining. The pertinent regulations state in part:

A supplemental application should be submitted for any change beyond the variations provided for in the application * * * that may alter the conditions of use, the labeling, the safety, identity, strength, quality or purity of the drug * * *. Labeling changes include deviations from the authorized brochure in any mailing or promotional piece used after the drug is placed on the market. When necessary for the safety of the drug, a supplemental application may be required to specify a period of time within which the proposed change will be made; and in such case the distribution of the drug after such time without such change constitutes distribution without an effective new-drug application. If a material change is made in the * * * labeling or advertising[ ] from the representations in an effective application for a new drug, and the drug is marketed before a supplement is effective for such change, the application may be suspended under § 130.27 on the grounds that it contains an untrue statement of a material fact. [21 C.F.R. § 130.9(a) (I960).]

Lederle also claims that warning without prior FDA approval would have violated regulations governing certification of batches of antibiotics, which stated:

(b) A certificate shall cease to be effective:

(2) With respect to any immediate container * * * when its label or labeling is altered, mutilated, destroyed, obliterated, or removed in whole or in part, or ceases to conform to any labeling requirement prescribed by the regulations in this part, except that:

(i) If the drug in such container is repacked * * *, and certification of the batch thus made is requested, such certificate shall continue to be effective for a reasonable time * * *; [or]

********

(iii) If its label or labeling is removed in whole or in part for the purpose of relabeling and supplemental certification of the relabeled drug is requested * * *. [21 C.F.R. § 146.4 (1955).]

According to Lederle, compliance with the obligation under New Jersey law to communicate a warning based on subsequently-acquired actual or constructive knowledge of a danger “as soon as reasonably feasible,” Feldman I, supra, 97 N.J. at 456, 479 A.2d 374, would have placed it in violation of the federal statutes and regulations if the warning had been given without prior FDA approval. Relying heavily on subsequent amendments and statements regarding the labeling regulations and the FDA’s interests with respect to drugs, the Appellate Division agreed, concluding that “the clear wording of [section 130.9(a) ] required Lederle to seek the approval of the FDA to change the package inserts dispensed with the drug.” 234 N.J.Super. at 588, 561 A.2d 288. The court felt constrained to conclude, based on the jury’s findings on when Declomycin was defective, that the jury had found liability based on Lederle’s failure to warn during the period it had corresponded with the FDA — November 1962 to December 1963. Id. at 573, 561 A.2d 288. The court then held that principles of conflict preemption precluded the assessment of liability for failure to warn without prior approval during that period.

Implicit in the Appellate Division’s conclusion is the notion that compliance with the letter of section 130.9(a) precludes finding for plaintiff on her strict-liability claim for failure to warn. Reading that provision in the context of the FDCA, however, and recognizing, as found by the Appellate Division, that “Congress’ overriding purpose in enacting the FDCA was to protect consumers from dangerous drugs and antibiotics,” id. at 581, 561 A. 2d 288, we are satisfied that federal law did not clearly require that Lederle obtain prior approval from the FDA before warning of a known or knowable danger. Accordingly, we find nothing in the federal scheme to support the assertion that manufacturers of prescription drugs and antibiotics who literally comply with that isolated provision must be immune from state tort liability for injuries caused by their products. In the absence of a clear and manifest purpose to preclude the traditional workings of the tort compensation system, we find no conflict and hence no preemption.

We conclude that there is not a sufficient basis on which to find a direct conflict between state and federal law. The correspondence between Lederle and the FDA in 1962 and 1963 does not foreclose a finding either that state damage actions could act as compensatory supplements to the existing regulatory framework or that the FDA had neither considered nor addressed the preemptive effect of the regulations at that time. In light of the Supreme Court’s concern, expressed most recently in English and ARC America Corp., that injured plaintiffs not be denied a remedy in the absence of a clearly-expressed intention, we adopt the reasoning of Abbot, Mazur, and Ferebee here. Applying their reasoning will advance the primary purposes of both federal and state law, respectively, protecting the public health and compensating those injured when that protection fails, without compelling drug manufacturers to violate federal statutes or regulations.

—C—

The FDCA “as a whole was designed primarily to protect consumers from dangerous products.” United States v. Sullivan, 332 U.S. 689, 696, 68 S.Ct. 331, 335, 92 L.Ed. 297, 303 (1948). We continue to believe, as we stated in Feldman I, that for the FDA to have prevented a drug manufacturer from warning the public of a newly-discovered danger pending development of unequivocal factual evidence of adverse reaction in man “would seem anomalous.” 97 N.J. at 459, 479 A.2d 374. A direct conflict is not clear from the evidence presented — or attempted to be presented — at trial. Dr. Swanzey testified only to an industry understanding that the FDA regulations required prior approval. Dr. Goddard’s report indicated that he believed the regulations required prior approval, but the relevant time period for this case was before his tenure as commissioner. Furthermore, his testimony at the Evidence Rule 8 hearing indicated that the labeling regulations had not been enforced before his arrival. The assertion that Lederle would have been subject to punishment for “misbranding” or would have had its product barred from the market if it had added an unapproved warning is based merely on Lederle’s interpretation of the regulations then in effect. Lederle presents no evidence indicating that the FDA ever took such action for adding a warning suggesting a limitation on use rather than an unapproved representation of a benefit, nor does the record reflect any statement by the FDA to the effect that it would have taken action had a manufacturer attempted to warn without prior approval.

Lederle relies heavily on the modification of the new-drug labeling regulations in 1965 and subsequent statements of the FDA to support its argument that Congress and the FDA intended that modification of labeling without prior approval had not been allowed previously, namely, at the time plaintiff had ingested the drug. The relevant FDCA-enforcement regulations were amended in 1965 to permit expressly “placpng] into effect at the earliest possible time” proposed additions to labeling “of additional warning, contraindication, side-effect, and precaution information.” 30 Fed.Reg. 993 (1965) (codified at 21 C.F.R. § 130.9(d)). The amendment went on to add:

It will be the policy of the Food and Drug Administration to take no action against a drug or applicant solely because changes of the kinds described in paragraph (d) of this section are placed in effect by the applicant prior to [its] receipt of a written notice of approval of the supplemental new drug application. [Ibid, (codified at 21 C.F.R. § 130.9(e)).]

The additions to section 130.9 were made effective immediately on publication in the Federal Register because they were in the interest of “drug safety” and “the public health, [were] noncontroversial, and relax[ed] existing requirements.” Ibid. The regulations controlling antibiotics were similarly modified in 1966 to permit dissemination of modified labeling without awaiting advance approval. See 31 Fed.Reg. 11,415 (1966).

Although we recognize that subsequent actions of an agency are relevant to determining prior intent, see Grove City College v. Bell, 465 U.S. 555, 567, 104 S.Ct. 1211, 1218, 79 L.Ed. 2d 516, 528 (1984), we do not agree that the conclusion that Lederle asserts necessarily follows. It contends that the modification shows that independent action was not permitted under the former regulations. An equally-compelling conclusion, however, is that the FDA had not addressed itself to the issue before. Cf. 3A Frumer & Friedman, Products Liability § 50.-03[1], 50-255 n. 37 (1990) (“One could argue that the changes made in § 130.9 in 1965 * * * indicate that FDA approval of precautionary information was required prior thereto. One could also argue that the change in language was meant to clear up a misconception.”). Arguably, then, on squarely considering the issue, the FDA determined that warning of possible dangerous side effects “at the earliest possible time,” 30 Fed.Reg. 993 (1965), was consistent with its primary purpose to protect the public health.

There is additional support for that conclusion. The 1965 modifications did not materialize out of a vacuum. The changes were made to implement the Kefauver-Harris Drug Amendments enacted on October 10, 1962. See U.S. Food and Drug Administration, Annual Reports 1950-197.# 374-75, 480-81, 527-28 (Dep’t of Health, Education and Welfare 1976). The FDA understood those amendments to require that prescription-drug advertisements “contain a brief summary of information as to adverse side effects of the drug and warnings of when it should not be administered.” Id. at 375. Dr. Goddard testified that the FDA regulations had not been enforced prior to his appointment as commissioner. That inaction could be explained rationally as recognition that the regulations in effect did not reflect the requirements of the FDCA as amended. The 1965 modifications to the regulations, then, demonstrate not an intent to require FDA pre-approval of warnings prior to 1965 but rather only an effort to clarify that in accordance with the purposes of the FDA, warnings of side effects were required. See 25 Fed.Reg. 12,595 (1960) (regulations governing labeling of new drugs were amended in 1960 for the express purpose of “requiring manufacturers to furnish adequate information for the professional use of prescription drugs and devices”).

When the issue is viewed as which party should bear the loss occasioned by a product marketed without warning of its dangerous propensities, Lederle’s contention based on the subsequent revision of the labeling regulations is even less persuasive. The 1965 modification and the pre-existing regulations are equally mute on the intention to deny compensation to persons injured by the use of antibiotic drugs. Lederle has not presented any evidence — such as legislative history or an administrative decision — displaying a congressional intent to preempt all or any methods of tort compensation. The majority in Silkwood found no inconsistency in letting persons injured by nuclear hazards recover under state tort law despite Congress’ express intent to have the Nuclear Regulatory Commission exclusively regulate the safety of nuclear facilities. 464 , 104 S.Ct. at 626, 78 L.Ed.2d at 458. Notably, the dissenting justices agreed concerning the award of compensatory damages. See id. at 263-64, 104 S.Ct. at 629, 78 L.Ed.2d at 462 (Blackmun, J., dissenting) (“Because the Federal Government does not regulate the compensation of victims, and because it is inconceivable that Congress intended to leave victims with no remedy at all, the pre-emption analysis established by [Pacific Gas & Electric Co. v. State Energy Resources Conservation & Development Commission, 461 U.S. 190, 103 S.Ct. 1713, 75 L.Ed.2d 752 (1983),] comfortably accommodates — indeed it compels — the conclusion that compensatory damages are not preempted whereas punitive damages are” (footnote omitted).); id. 464 U.S. at 275, 104 S.Ct. at 635, 78 L.Ed.2d at 469 (Powell, J., dissenting) (“Where injury is sustained as a result of the operation of a nuclear facility, it is not contested that compensatory damages under state law properly may be awarded.”). We reach a similar conclusion here.

Finally, we note that a finding of preemption would leave plaintiff remediless, a fact that, based on Silkwood and Dewey, strengthens the presumption against preemption. See Silk-wood, supra, 464 U.S. at 251, 104 S.Ct. at 623, 78 L.Ed.2d at 454; Dewey, supra, 121 N.J. at 84-85, 577 A.2d 1239. However the action is viewed, the revision does not display a “clear and manifest” intent to preclude either (1) warning without prior FDA approval or (2) determining under state law that the manufacturer should bear the loss caused by a defective product, namely, a product marketed without a warning of a known or knowable dangerous side effect.

The Appellate Division, interpreting two cases from other jurisdictions addressing the regulations in effect at the time of plaintiffs ingestion of Declomycin, found that both cases concluded that FDA approval was required prior to making a labeling change. 234 N.J.Super, at 588, 561 A.2d 288. One case, Roginsky v. Richardson-Merrell, Inc., 378 A.2d 832 (2d Cir.1967), assumed that advance permission from the FDA was required apparently because neither party had raised the issue. Id. at 835, 848. That court did not render a specific finding, nor did it indicate any authority compelling its conclusion. The other case merely cited Roginsky. See Miller v. Upjohn Co., 465 So.2d 42 (Ct.App.), writ denied, 467 So.2d 533 (La.1985). To the extent those cases addressed preemption of failure-to-warn claims, the analyses are uncompelling, and we decline to follow them.

The Appellate Division also strongly emphasized the FDA’s interest in “rational prescribing.” See 234 N.J.Super. at 593-95, 561 A.2d 288. However, the Commissioner of the FDA has stated that “[i]t is not the intent of the FDA to influence the civil tort liability of the manufacturer.” 44 Fed.Reg. 37,437 (1979). In light of that unequivocal statement, we are unpersuaded that the asserted interest in rational prescribing precludes imposition of liability. Lederle’s correspondence and internal documents establish that it knew or believed that there was an adverse causal association between Declomycin and tooth-staining. Lederle knew or believed that a portion of Declomycin users would be permanently injured by using the product as marketed. We are convinced that marketing Declomycin with that knowledge and belief constitutes the very conduct that the FDA intended not to absolve.

Finally, we note that Dr. Goddard testified that a manufacturer remained free to choose not to distribute a drug, an option cited in Dewey and Ferebee as additional support for a finding of no conflict. Lederle believed that a warning was necessary and proper for Declomycin. We find no basis to conclude that the FDA through its regulations mandated that Lederle disregard its determination and continue to produce a drug that it believed to be unsafe as distributed. The testimony of Dr. Goddard persuasively suggests a contrary conclusion. Irrespective of what the regulations may have required with regard to changes in labeling, we find no basis for concluding that Lederle was required to continue marketing Declomycin in forms and packaging intended for use by those it believed to be at risk — or indeed to continue marketing at all. Such a requirement would conflict with the predominant, express purpose for which the FDA was created and for which the new drug regulations were enacted.

We also note that Lederle is not faced with the Hobson’s choice of either complying with federal regulations and continuing to be subject to damages in state tort actions or providing additional warnings and thereby violating federal law. The regulations in question have long since been changed expressly to allow pharmaceutical companies to implement necessary changes in labeling while a supplemental new-drug application is pending. See 30 Fed.Reg. 993 (1965). Furthermore, the present regulations governing labeling of prescription drugs require that the labeling “describe serious adverse reactions and potential safety hazards, [and] limitations in use imposed by them.” 21 C.F.R. § 201.57(e) (1990). Interestingly, that provision states that “labeling shall be revised to include [such] a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.” Ibid.

The issue then is what choices, if any, did Lederle have in 1962 and 1963. Even if we assume Lederle could not have provided a warning, an assumption we find unsupported by the evidence, it could have suspended production of Declomycin for what it termed the “probably * * * short period of time” before which Lederle anticipated that that drug too would be “officially implicated with tooth staining.” Alternatively, Lederle could have quite reasonably and responsibly removed from the market those forms and methods of packaging of Declomycin that were geared toward pediatric use. It could have raised the price as a form of loss-spreading insurance against claims. Lederle also could have continued to press for FDA approval of a warning for Declomycin after the administration’s initial response declining to change its official position. (The record is conspicuously silent on any continuing efforts by Lederle to confirm the association of Declomycin with tooth staining or to gain FDA sanction of a warning for Declomycin. Cf. Feldman I, supra, 97 N.J. at 453, 479 A.2d 374 (“at least in some fields, such as those impacting on public health, a manufacturer may be expected to be informed and affirmatively to seek out information concerning the public’s use of its own product”).) The suggestion that Lederle was in some way compelled to continue distributing a drug without warning of the strong likelihood of serious side effects for some child users and that Congress and the FDA intended that it would be immune from liability for doing so cannot be reconciled with the primary purpose of the FDA to promote and protect the health of the citizens of the United States.

We find nothing in the record to justify a belief that Declomycin was different from the other tetracycline analogues in such a way that the discoloration side effect was unlikely to materialize. In fact, Lederle believed the evidence respecting Declomycin to be inevitably forthcoming “within a short period of time.” The obvious reason for the lack of sufficient information on Declomycin was that Declomycin had been developed and introduced to the market later than the other members of the family of tetracyclines. The nature of the side effect precluded conclusive scientific information from being available until the permanent teeth of pediatric patients began to erupt. The issue, then, was not whether there would be evidence of tooth discoloration associated with Declomycin sufficient to justify the FDA in requiring a warning, but rather when such evidence would be available.

Simply stated, immunizing a drug manufacturer against liability for marketing a product without a warning of a known or knowable risk is in conflict with Congress’ well-recognized purpose in enacting the FDCA, particularly as amended in 1962. We will not recognize such an anomalous claim of immunity based solely on a manufacturer’s representations of the industry’s belief. Here the evidence was conclusive that tetracycline analogues were not safe for children and that all other tetracyclines in existence long enough to provide data did not furnish adequate information as labelled previously. The exclusion of Declomycin from the group approved for a label change was an unfortunate turn of events. We decline to visit the harm inflicted by a product on an innocent end-user by holding as a matter of law that Congress and the agency charged with protecting the public health intended to absolve from liability a manufacturer aware of the risk of that very harm.

We recognize that (assuming the price of Declomycin did not already include a “buffer factor” for unforeseen costs, an uncompelling assumption at best) Lederle might have had to increase the price of the product in order to absorb and spread the cost of the harm. So be it. Unlike the vaccines reviewed by the dissent, see post at 134-137, 592 A.2d at 1185-1187, Declomycin was not a wonder drug, without substitute or equipollent. The FDA “determination” in this case was really a non-decision — namely, that the evidence was not yet unequivocal or “substantial” as defined in the FDCA. It does not reflect a carefully-considered risk-benefit analysis of Declomycin’s utility such that it should shield Lederle from plaintiffs claims for the harm caused by Declomycin. Lederle, believing that a warning would soon be required and that pediatric use of Declomycin would have harmful side effects, could not reasonably sit idly by, immunized from responsibility for those anticipated repercussions by legislation intended to promote the public health. See MacDonald v. Ortho Pharmaceutical Corp., supra, 394 Mass. 131, 475 N.E.2d 65.

IV

The record does not contain any formal administrative decision demanding deference from this Court. See Young v. Community Nutrition Inst., 476 U.S. 974, 106 S.Ct. 2360, 90 L.Ed.2d 959 (1986). The subsequent amendments relied on so heavily by Lederle are susceptible of varying interpretations supporting both parties’ positions. A finding of direct conflict is not compelled. This Court will not seek out a basis for such a finding. See English v. General Elec. Co., supra, — U.S. at -, 110 S.Ct. at 2280, 110 L.Ed.2d at 81.

The presence of the following factors reinforces the traditional presumption against preemption: that there was no explicit provision for preemption of state tort claims; that the subject matter infringes on the State’s inherent powers to protect and promote the health and safety of its citizens; and that preemption would effectively eliminate all means of recourse for the plaintiff. See Dewey, supra, 121 N.J. at 84-85, 577 A.2d 1239; Forster v. R.J. Reynolds Tobacco Co., 423 N.W 2d 691 (Ct.App. 1988) , aff'd in part and rev’d in part, 437 N. W.2d 655 (Minn. 1989) . If there had been a need to immunize prescription drug and antibiotic manufacturers from tort liability, the determination of that need should have been “made by Congress in an unambiguous mandate and not by the courts.” Forster, supra, 423 N. W. 2d at 701. To date Congress has not seen fit to express such a mandate. We will not do so in its stead.

V

As a final point in opposition to this appeal, Lederle raises the contention that “[i]f this case were again retried, there is no way that plaintiff could prevail.” Lederle bases that contention on the hopeful conclusion that the rebuttable presumption created by N.J.S.A. 2A:58C-4 will be conclusive on remand. We believe Lederle overstates the import of the statute.

Section four of the Products Liability Law, N.J.S.A. 2A:58C-4, creates a rebuttable presumption that a warning or instruction is adequate “if the warning or instruction given in connection with a drug * * * has been approved or prescribed by the federal Food and Drug Administration.” The section also defines adequate warning as follows:

An adequate product warning or instruction is one that a reasonably prudent person in the same or similar circumstances would have provided with respect to the danger and that communicates adequate information on the dangers and safe use of the product, * * * in the case of prescription drugs, taking into account the characteristics of, and the ordinary knowledge common to, the prescribing physician. [Ibid.}

Because the legislation affects the weight to be given FDA approval but does not change the burden of proof, it would apply to this cause on remand. N.J.S.A. 2A:58C-1 (section 8, not codified, provides for immediate effect); see Shackil v. Lederle Laboratories, 116 N.J. 155, 214, 561 A.2d 511 (1989) (O’Hern, J., dissenting).

The actual effect of the statute, however, is less clear. Its plain language defies the conclusion that the presumption cannot be overborne. Once the determination goes to the jurors, irrespective of an instruction from the court, they are free to disregard evidence of “approval” by the FDA. Cf. McCormick on Evidence § 344, at 978-79 (E. Cleary 3rd ed. 1984) (discussing instructions to jury when there is a presumption). Moreover, the statutory provision was enacted in the context of present FDCA, PHSA, and regulatory provisions that explicitly require warning of possible adverse side effects as soon as reasonably feasible and based on “reasonable evidence.” See 21 C.F.R. § 201.57(e) (1990). Consequently, under the unique circumstances of this case, compliance with the “determination” of the FDA not to require a warning for Declomycin due to the lack of “unequivocal factual evidence of adverse reaction in man,” although evidence of the adequacy of the labeling, should not be accorded the same presumptive weight now given to warnings approved or prescribed by that agency, and certainly does not create a conclusive presumption that the labeling contained an adequate warning.

VI

We hold that Lederle has failed to establish that civil tort liability is precluded because of an actual conflict with federal law and regulations. The case is remanded to the Appellate Division for consideration of those issues raised before that court but not addressed by it.